Impact of Antibiotic Therapy on the Upper Respiratory Tract and Gut Mycobiome in Patients with Cystic Fibrosis.

Abstract

Patients with cystic fibrosis (CF) are frequently exposed to antibiotic treatments, which can alter the fungal communities (mycobiome) across their mucosal sites. This pilot study investigated the impact of antibiotic exposure on the mycobiome by analyzing fungal community dynamics in the upper respiratory- (nasal lavage) and gastrointestinal- (stool samples) tracts of 12 patients with CF following (a) long-term antibiotic treatment over a three-year period and (b) short-term antibiotic therapy during acute pulmonary exacerbations. Mycobiome profiles of the samples obtained from 38 healthy individuals were also analyzed and used for comparison purposes. The ITS1 region of the fungal rRNA gene cluster was sequenced to characterize and quantify the fungal community composition in both cohorts. Compared to healthy controls, samples from the patients with CF who had undergone long-term antibiotic treatment revealed a significantly increased fungal biomass in both sino-nasal and stool samples. Moreover, diversity metrics revealed significant differences in nasal lavage samples, whereas the stool samples showed no significant variation. Candida spp. was significantly enriched in both nasal and stool samples from CF patients. Further analyses demonstrated a strong positive correlation between the relative abundance of Candida spp. and the cumulative antibiotic intake over the three-year period in sino-nasal samples, but not in stool samples. Acute antibiotic treatment during a pulmonary exacerbation episode also led to a marked increase in the abundance of Candida spp. in sino-nasal samples. These findings highlight the increased sensitivity of the sino-nasal mycobiome to both chronic and acute antibiotic exposure in CF patients, as characterized by a site-specific fungal overgrowth, particularly of Candida spp.